Pflügers Archiv : European journal of physiology
-
Cooling is sensed by peripheral thermoreceptors, the main transduction mechanism of which is probably a cold- and menthol-activated ion channel, transient receptor potential (melastatin)-8 (TRPM8). Stronger cooling also activates another TRP channel, TRP (ankyrin-like)-1, (TRPA1), which has been suggested to underlie cold nociception. This review examines the roles of these two channels and other mechanisms in thermal transduction. ⋯ Cold can also cause pain: the transduction mechanism is uncertain, possibly involving TRPM8 in some neurones, but another candidate is TRPA1 which is activated in expression systems by strong cooling. However, native neurones that appear to express TRPA1 respond very slowly to cold, and TRPA1 alone cannot account readily for cold nociceptor activity or cold pain in humans. Other, as yet unknown, mechanisms of cold nociception are likely.
-
The endothelial cells (ECs) form a semipermeable barrier between the blood and the tissue. An important function of the endothelium is to maintain the integrity of the barrier function of the vessel wall. Ca(2+) signaling in ECs plays a key role in maintaining the barrier integrity. ⋯ Inflammatory mediators such as thrombin, histamine, bradykinin, and others increase endothelial permeability by actin polymerization-dependent EC rounding and formation of inter-endothelial gaps, a process critically dependent on the increase in EC cytosolic [Ca(2+)] ([Ca(2+)](i)). Increase in endothelial permeability depends on both intracellular Ca(2+) release and extracellular Ca(2+) entry through TRPC channels. This review summarizes recent findings on the role of TRPC channels in the mechanism of Ca(2+) entry in ECs, and, in particular, the role of TRPC channels in regulating endothelial barrier function.
-
In healthy humans, changes in cardiac output are commonly accommodated with minimal change in pulmonary artery pressure. Conversely, exposure to hypoxia is associated with substantial increases in pulmonary artery pressure. In this study we used non-invasive measurement of an index of pulmonary artery pressure, the maximum systolic pressure difference across the tricuspid valve (DeltaPmax), to examine the pulmonary vascular response to changes in blood flow during both air breathing and hypoxia. ⋯ In this group DeltaPmax rose progressively from 21 mmHg to 37 mmHg over 8 h. By comparing diurnal variations in DeltaPmax during air breathing with changes in DeltaPmax during hypoxia in the same eight individuals, we concluded that only approximately 5% of the changes in DeltaPmax during hypoxia could be attributed to concurrent changes in cardiac output. The low sensitivity of DeltaPmax to changes in cardiac output makes it a useful index of hypoxic pulmonary vasoconstriction in healthy humans.
-
The present study addressed the question of whether nitric oxide (NO) participates in regulation of osmotic water permeability in the urinary bladder of the frog Rana temporaria L. Experiments were carried out on isolated, paired hemi-bladders filled with amphibian Ringer solution diluted 1:10 with distilled water. Sodium nitroprusside (SNP, 125-250 micro M), an NO donor, markedly attenuated the increase of osmotic water flow elicited by arginine-vasotocin (AVT) (AVT 10(-10) M: 2.20+/-0.26; AVT plus 200 micro M SNP: 1.21+/-0.15 micro l/min cm(2), n=20, P<0.001). ⋯ Immunohistochemistry of urinary bladder slices with antibodies against different types of NO synthase (NOS) revealed a positive immunostaining for neuronal NOS (nNOS) in the mucosal epithelium. These results suggest that in the frog urinary bladder endogenous NO is involved in regulation of water osmotic permeability. NO inhibits the AVT-induced increase of water flow at least partly by activation of PKG, which interferes with the hydroosmotic effect of AVT probably at (a) post-cAMP step(s).
-
The electroneutral cation-chloride-coupled cotransporter gene family ( SLC12) was identified initially at the molecular level in fish and then in mammals. This nine-member gene family encompasses two major branches, one including two bumetanide-sensitive Na(+)-K(+)-2Cl(-) cotransporters and the thiazide-sensitive Na(+):Cl(-) cotransporter. Two of the genes in this branch ( SLC12A1 and SLC12A3), exhibit kidney-specific expression and function in renal salt reabsorption, whereas the third gene ( SLC12A2) is expressed ubiquitously and plays a key role in epithelial salt secretion and cell volume regulation. ⋯ The transported substrates of the remaining two SLC12 family members, SLC12A8 and SLC12A9, are as yet unknown. Inactivating mutations in three members of the SLC12 gene family result in Mendelian disease; Bartter syndrome type I in the case of SLC12A1, Gitelman syndrome for SLC12A3, and peripheral neuropathy in the case of SLC12A6. In addition, knockout mice for many members of this family have generated important new information regarding their respective physiological roles.